Genetic Variant FAM47C:p.Arg36Ser (chrX-37008518-G-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001013736.3(FAM47C):c.108G>T(p.Arg36Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,211,607 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., 4 hem., cov: 25)

Exomes 𝑓: 0.000014 ( 0 hom. 2 hem. )

Consequence

FAM47C
NM_001013736.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.640

Variant links:

Genes affected

FAM47C (HGNC:25301): (family with sequence similarity 47 member C) This gene encodes a product belonging to a family of proteins with unknown function. The coding sequence of this family member includes several tandemly repeated regions. [provided by RefSeq, Sep 2011]

FAM47C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.017594546).

BS2

High Hemizygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM47C	NM_001013736.3 link	c.108G>T	p.Arg36Ser	missense_variant	Exon 1 of 1	ENST00000358047.5	NP_001013758.1	Q5HY64

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM47C	ENST00000358047.5 link	c.108G>T	p.Arg36Ser	missense_variant	Exon 1 of 1	6	NM_001013736.3	ENSP00000367913.3		Q5HY64

Frequencies

GnomAD3 genomes

AF:

0.0000794

AC:

AN:

113355

Hom.:

Cov.:

AF XY:

0.000113

AC XY:

AN XY:

35483

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00252

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000933

AC:

AN:

182120

Hom.:

AF XY:

0.0000450

AC XY:

AN XY:

66726

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00123

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000137

AC:

AN:

1098199

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

363553

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000497

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000794

AC:

AN:

113408

Hom.:

Cov.:

AF XY:

0.000113

AC XY:

AN XY:

35546

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00253

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000718

ExAC

AF:

0.0000989

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 29, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.108G>T (p.R36S) alteration is located in exon 1 (coding exon 1) of the FAM47C gene. This alteration results from a G to T substitution at nucleotide position 108, causing the arginine (R) at amino acid position 36 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.52

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.80

CADD

Benign

5.8

DANN

Uncertain

0.98

DEOGEN2

Benign

0.012

FATHMM_MKL

Benign

0.0026

LIST_S2

Benign

0.46

M_CAP

Benign

0.00073

MetaRNN

Benign

0.018

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.026

Sift

Benign

0.067

Sift4G

Uncertain

0.042

Polyphen

0.92

Vest4

0.13

MutPred

0.37

Gain of phosphorylation at R36 (P = 0.0069);

MVP

0.12

MPC

0.31

ClinPred

0.25

GERP RS

0.46

Varity_R

0.33

gMVP

0.061

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over